Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

ABSTRACT: Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect. By performing a high-throughput screening of epigenetic and FDA-approved compounds in a co-transfection model of wild-type and mutant p63, we found that two compounds, Doxorubicin and Epirubicin, alleviate protein aggregation and restore p63 transactivation function. Moreover, treatment with these compounds reduced prot

SUBMITTER: Boncimino F 

PROVIDER: S-EPMC11762975 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature